Pathophysiology
Summary
Qualitative platelet dysfunction is marked by an extended bleeding time, despite normal levels of platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT). This type of dysfunction manifests as ‘platelet-type' bleeding, including symptoms like easy bruising, petechiae, and epistaxis. Various conditions can cause this qualitative platelet dysfunction: Uremia from kidney disease disrupts platelet aggregation and adhesion due to uremic toxins, leading to similar bleeding symptoms. Trauma can impair platelet function through mechanisms such as lactic acidosis and temperature dysregulation. Diabetes mellitus can also cause qualitative platelet dysfunction, as chronic hyperglycemia results in hyperactive platelets, elevating the risk of thrombosis and myocardial infarction.
Inherited disorders also contribute to qualitative platelet dysfunction. Bernard-Soulier syndrome is an autosomal recessive disorder where a deficiency in glycoprotein 1b (GP1b) receptors prevents platelets from adhering to von Willebrand factor (vWf), impairing platelet plug formation and causing excessive bleeding. This syndrome features giant platelets in peripheral blood and a negative ristocetin test. Glanzmann thrombasthenia is an autosomal recessive condition that involves dysfunctional glycoprotein IIb/IIIa (GP2b/3a), preventing fibrinogen from binding to platelets and reducing platelet plug formation. As vWF and Gp1b are unaffected, the ristocetin test is normal glanzmann thrombasthenia.
Wiskott-Aldrich syndrome is an X-linked recessive disorder caused by mutations in the Wiskott-Aldrich syndrome protein (WASP). This syndrome is unique as it causes both quantitative and qualitative platelet deficiencies, resulting in thrombocytopenia. The small and deformed platelets in Wiskott-Aldrich syndrome phagocytosed by splenic macrophages which contributes to thrombocytopenia. Wiskott-Aldrich presents with eczema and immunodeficiency due to a combined T cell and B cell deficiency.
Lesson Outline
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FAQs
Qualitative platelet disorders can arise from various factors such as uremia due to kidney disease, trauma, and diabetes mellitus. In uremia, toxins interfere with platelet aggregation and adhesion, leading to ‘platelet-type' bleeding. Trauma-related conditions like lactic acidosis or temperature dysregulation can similarly impair platelet function. In diabetes mellitus, chronic hyperglycemia disrupts signaling pathways, making platelets hyperactive and increasing the risk of thrombus formation.
In qualitative platelet dysfunction, bleeding time is typically prolonged. This occurs due to impaired platelet function rather than a decrease in platelet quantity. Despite having normal platelet counts, normal prothrombin time (PT), and normal activated partial thromboplastin time (aPTT), individuals may experience increased bleeding from skin and mucous membranes. Symptoms can include easy bruising, petechiae, and nosebleeds (epistaxis).
Bernard-Soulier syndrome is an inherited qualitative platelet disorder caused by a deficiency in glycoprotein 1b (GP1b) receptors on the platelet surface. These receptors are essential for platelets to adhere to von Willebrand factor (vWf), a key step in forming a platelet plug. The absence of GP1b receptors prevents platelet adhesion to vWf, leading to excessive bleeding. Additionally, this syndrome is characterized by the presence of unusually large platelets in the peripheral blood.
Glanzmann thrombasthenia is another inherited qualitative platelet disorder characterized by dysfunctional glycoprotein IIb/IIIa (GP2b/3a) on the platelet surface. This dysfunction prevents fibrinogen from binding to the platelets, impairing the formation of a platelet plug and leading to a ‘platelet-like' bleeding pattern. Notably, the ristocetin test is usually positive in Glanzmann thrombasthenia, as von Willebrand factor and GP1b function normally in this condition.
Wiskott-Aldrich syndrome is a unique inherited disorder that causes both quantitative and qualitative platelet deficiencies. It results from mutations in the Wiskott-Aldrich Syndrome protein (WASP), a cytoskeletal protein found in platelets, B-cells, and T-cells. Wiskott-Aldrich syndrome leads to thrombocytopenia, and produces small, deformed platelets that are less effective in clotting. These platelets are often phagocytosed by splenic macrophages, exacerbating the thrombocytopenia. Additionally, the syndrome is associated with immunodeficiency, affecting both T and B cells.
